The histologic fetal inflammatory response and neonatal outcomes: systematic review and meta-analysis.

OBJECTIVE: To investigate the prognostic role of concomitant histologic fetal inflammatory response with chorioamnionitis on neonatal outcomes through a systematic review and meta-analysis of existing literature.

DATA SOURCES: The primary search was conducted on October 17th , 2021, and it was updated on May 26th , 2023, across four separate databases (MEDLINE, CENTRAL, Embase, and SCOPUS) without using any filters.

STUDY ELIGIBILITY CRITERIA: Observational studies reporting obstetrical and neonatal outcomes of infant-mother dyads with histological chorioamnionitis and histologic fetal inflammatory response in comparison to histological chorioamnionitis alone were eligible. We included studies that enrolled only preterm neonates, born before the 37th gestational week, or very low birth weight neonates (birthweight < 1500 g). The protocol was registered with the International Prospective Register of Systematic Reviews (CRD42021283448).

STUDY APPRAISAL AND SYNTHESIS METHODS: The records were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random-effect model-based pooled odds ratios with corresponding 95% confidence intervals were calculated for dichotomous outcomes.

RESULTS: In total of 50 studies were identified. Quantitative analysis of 14 outcomes was performed. We conducted subgroup analysis using mean gestational age of the studies, and we implemented the 28th gestational week as a cut off line. Among neonates with lower gestational ages, early-onset sepsis (pooled odds ratio 2.23; 95% confidence interval, 1.76-2.84). and bronchopulmonary dysplasia was associated (pooled odds ratio 1.30; 95% confidence interval, 1.02 to 1.66) with the histologic fetal inflammatory response. Our analysis showed that preterm neonates with a concomitant histologic fetal inflammatory response are more likely to develop intraventricular hemorrhage (pooled odds ratio 1.54; 95% confidence interval, 1.18 to 2.02) and retinopathy of prematurity (pooled odds ratio 1.37; 95% confidence interval, 1.03 to 1.82). Among infant-mother dyads with histologic fetal inflammatory response, the odds of clinical chorioamnionitis were almost three-fold higher (pooled odds ratio 2.99; 95% CI, 1.96 to 4.55) than in the histological chorioamnionitis alone group.

CONCLUSION: Investigating multiple neonatal outcomes, we found a statistically significant association in the case of four major morbidities: early-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage and retinopathy of prematurity.